The manufacturing of microfluidic devices by bonding the surfaces of two generally planar substrates together has been described in a number of publications.
U.S. Pat. No. 5,376,252 (Ekström et al.,) vaguely suggests in general terms that certain combinations of material might require gluing for joining the substrates together. In certain variants, walls projecting from the surface of the plastic substrate defined the open microchannel structure. The problems with clogging and the formation of irregularly occurring constrictions were never recognized.
U.S. Pat. No. 4,957,582 (Columbus) suggests to produce a microfluidic device comprising hydrophilic microchannels by using hydrophilic glues.
WO 9424900 (Öhman) suggests to use a gluing solution comprising (a) a solvent not dissolving the substrate surfaces, and (b) a gluing component capable of fusing with the substrate surfaces.
WO 9845693 and U.S. Pat. No. 6,176,962 (Soane et al.,) suggest to use adhesives in combination with particular protocols.
WO 9956954 (Quine) suggests bonding together two generally planar plastic substrates that has been apposed. Bonding is accomplished by heating one of the apposing substrate surfaces above its transition temperature without reaching the transition temperature of the other apposing substrate surface. The “non”-heated surface comprises microscale grooves that defines the stretches of the final microchannel structures. A heat-sensitive meltable texture of bonding material elevating from one of the surfaces could be present outside the grooves.
WO 0050871 (Dapprich) presents microfluidic devices that may be manufactured by adhering the surfaces of two essentially planar substrates to each other. One of the substrates has a microstructured surface that defines the microchannel structures of the final device.
WO 0154810 (Derand et al.,) suggests to thermolaminate a plastic cover to open microchannel structures that are manufactured in a plastic substrate and contain areas of different surface characteristics.
One important and common goal of WO 9424900, WO 9845693 (and U.S. Pat. No. 6,176,962), WO 9956954, WO 0154810, and U.S. Pat. No. 4,957,582 is to minimize irregular deformation of the microchannels caused by intrusion of bonding material or by heat deformation of the channel structures. None of publications account for utilizing channel walls (including rims) that project from the surface of a substrate to minimize the risk for intrusion of bonding material.
WO 9832535 (Lindberg et al.,) and WO 0197974 (Chazan et al.,) concern the problem of minimizing the negative effect of bond void when bonding two planar substrates together. Bond voids depends on irregularities in the surfaces, contaminating particles, unevenly applied pressure during the actual bonding step etc. Bond voids are primarily a problem when rigid substrate materials, such as glass, silicon, quartz, diamonds and certain plastics that have a pronounced rigidity, are combined with bonding processes not utilizing adhesives. The problem with bond voids is normally not at hand for plastic substrates, which typically are flexible. WO 9832535 (Lindberg et al.,) suggests that bond voids can be avoided if the walls of the microchannels are defined by projections in the surface of the substrate and if there are also separate projections defining spacing posts. WO 0197794 (Chazan et al.,) suggests that the disturbing effect of bond voids is avoided by including venting elements in the substrate surfaces in order to neutralize the disturbing effects bond voids might have on the microfluidic channels.
WO 0130490 (Schaevitz et al.,) describes improved sealings of openings in a microfluidic device comprising a number of microchannel structures. Each opening has a collar to which a lid is sealed. The lids are conformable and/or adhesive.
The kind of microfluidic devices defined above has previously been suggested for use as microlaboratories in which a plurality of similar analytical and/or preparative protocols that are in miniaturized form are carried out in parallel (one run per microchannel structure). When going down in channel sizes and liquid volumes, the demands on channel uniformity between different microchannel structures becomes extremely stringent in order to obtain reliable, reproducible and accurate results from the protocols.
The inventors have recognized that the conventional methods of the type described in the first paragraph under the heading “Technical Field” easily cause bonding material, in particular adhesives, to spread into the microchannels in an uncontrolled manner when the substrates are pressed together during the actual bonding process. The risk for creation of irregularly occurring constrictions and/or complete clogging of a microchannel structure is significant and increases with amount of bonding material, in particular liquid adhesives, and contact area between the two substrates. Thus, the first object of the invention aims at minimizing this kind of risks.
A second object is to increase the yield of functioning microchannel structures in microfluidic devices that comprise a plurality of microchannel structures, for instance 2, 3, 4, 5 or more microchannel structures. The yield in this context typically means that ≧70%, such as ≧85% or ≧95% or 100% of the microchannel structures in the final microfluidic device are functional, i.e., that they permit through flow of a liquid by having no substantial constriction and/or clogging caused by uncontrolled spreading of bonding material during the manufacturing step comprising bonding of the surfaces to each other. This object in particular applies in case the microchannel structures comprise parts in which the widths and/or depths are in the lower part of the largest of the ranges given above.
By applying an adhesive to one of the surfaces that are to be joined together there will be certain drawbacks. The adhesive will appear also on parts of the inner surfaces of the microchannel structures. This is mostly not desirable and may require post-modification of the inner surfaces. A simple method for avoiding this kind of drawback is desirable. A third object of the invention aims at minimizing this drawback.